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Decoding HIV Drug Resistance

OPINION By LOREEN WILLENBERG

Jan. 8, 2007 — Scientists have a potential new weapon for their fight against AIDS — a test that could tell doctors which drugs won't work for a given patient.

A new, highly sensitive test can detect tiny levels of drug-resistant HIV in the blood, say researchers at Duke University Medical Center. The test could help patients avoid medicine that would ultimately fail to fight their HIV infection. HIV can continue to spread and weaken a patient's immune system if it develops resistance to treatment medications. The treatment resistance, if unchecked and unnoticed, can make the progression from HIV to full-blown AIDS more likely.

Scientists know of about 30 mutations that can make HIV resistant to one of 20 drugs used to treat the infection. If doctors can identify which, if any, of those mutations are present on a given strain of HIV, they have a better chance of finding a drug that can successfully keep the virus in check.

Researchers hope this test will be the key to more effective and efficient treatments for HIV-infected patients, but this new test won't be ready for HIV patients anytime soon. Further studies need to confirm that the test is a reproducible one, something that labs across the country can carry out. Scientists don't know yet whether this test is easy and reliable enough for clinics to use.

Personal Perspective: A Possible Advance but Not an Answer

Any scientific advance in the suppression of HIV is welcome news.

An ultrasensitive test to detect drug-resistant strains of the virus will undoubtedly become a helpful tool in the complicated arsenal of treatment options. Since the virus is constantly mutating (RNA viruses like HIV mutate rapidly — 10 billion HIV-1 virus particles are generated daily), how well can this test keep up with the ever-changing virus?

Perhaps this ultrasensitive test would be more effective if there were more classes of drugs available.

I am an HIV-positive woman, and although I do not speak directly from firsthand experience (I've never needed medications), I can share observations based on my involvement with the HIV-affected community at large over the last 14 years.

An immediate benefit of this test would be knowledge for both doctor and patient that would improve treatment and eliminate the time and pain of experimenting with ineffective drugs.

The Treatment Waiting Game

The way treatment usually works now, a doctor prescribes a drug (or drugs) and waits three months to request lab tests that check immune cell counts and viral loads to see whether the prescriptions are actually working. If tests show that the drugs aren't effectively fighting the virus, it's back to the drawing board. Prescribe a new drug. Wait three months. Repeat process.

Different drug combinations work in some individuals, some do not. For a given patient's particular (and mutated) strain of HIV, this same process is repeated 10, 20 or more times.

In the case of a newly diagnosed individual, when the viral activity is typically highest, the right treatment regimen for their specific HIV type can provide early and consistent suppression of the virus (generally recommended), thus streamlining treatment and maximizing viral suppression. This new test could, in theory, make it easier for doctors to discover that "right" treatment.

In the case of those infected over many years, and who may be running out of treatment options, pinpointing the exact resistant mutation can calm a patient's overwhelming fear of impending demise — and can become an ultimate provider of hope.

Accurate and efficient streamlining of the treatment regimen can also reduce the risk of drug toxicity from a less-than-ideal drug cocktail. Drug toxicity can cause damage to kidneys and the liver, and allergic reactions like severe diarrhea or yellowed skin.

It is also important to remember the human factor in this equation — a test like this one would bring medical and mental relief to the patients who are helped by it.

In a recent article published by the Canadian AIDS Treatment Exchange (CATIE) on Dec. 22, 2006, entitled "A biological link between HIV and Depression," authors write that "dealing with medical needs — such as drug-related side effects and decisions about starting, switching and interrupting therapy — can be a great source of stress."

For an HIV-infected person, stress can be dangerously fatal.

Test Is Needed, and Hoped For

What I can speak to from direct and personal experience is this: Should the time arrive for me to begin a treatment regimen for HIV, I would be among those who exhibit a resistance to the drug indinavir (sold as Crixivan) because I carry a mutation located at position 46 on the genetic code.

What if I had this resistance and was unaware, while my physician continued to prescribe the drug that my virus could fight against?

This discovery does not answer every question but carries a lot of hope. As one doctor said to ABC News, "If we answer the questions and it works, I'd use it in a heartbeat."

For more information on HIV drug resistance, check out: http://www.hivdrugresistance.com/

Loreen Willenberg is a member of the Sacramento HIV Health Services in California. She was diagnosed with HIV in 1992. Contributions to this article were also made by John Martin, Kansas City Planning Council member; and Dave Casey, AIDS Treatment Activist's Coalition (ATAC) and Sacramento HIV Health Services Planning Council member.


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